title: Differential effects of polyphenols on proliferation and apoptosis in human myeloid and lymphoid leukemia cell lines.
abstract: BACKGROUND
  Mortality rates for leukemia are high despite considerable improvements in treatment. Since polyphenols exert pro-apoptotic effects in solid tumors, our study investigated the effects of polyphenols in haematological malignancies. The effect of eight polyphenols (quercetin, chrysin, apigenin, emodin, aloe-emodin, rhein, cis-stilbene and trans-stilbene) were studied on cell proliferation, cell cycle and apoptosis in four lymphoid and four myeloid leukemic cells lines, together with normal haematopoietic control cells.
  
  
  METHODS
  Cellular proliferation was measured by CellTiter-Glo(®) luminescent assay; and cell cycle arrest was assessed using flow cytometry of propidium iodide stained cells. Apoptosis was investigated by caspase-3 activity assay using flow cytometry and apoptotic morphology was confirmed by Hoescht 33342 staining.
  
  
  RESULTS
  Emodin, quercetin, and cis-stilbene were the most effective polyphenols at decreasing cell viability (IC50 values of 5-22 μM, 8-33 μM, and 25-85 μM respectively) and inducing apoptosis (AP50 values (the concentration which 50% of cells undergo apoptosis) of 2-27 μM, 19-50 μM, and 8-50 μM respectively). Generally, lymphoid cell lines were more sensitive to polyphenol treatment compared to myeloid cell lines, however the most resistant myeloid (KG-1a and K562) cell lines were still found to respond to emodin and quercetin treatment at low micromolar levels. Non-tumor cells were less sensitive to all polyphenols compared to the leukemia cells.
  
  
  CONCLUSIONS
  These findings suggest that polyphenols have anti-tumor activity against leukemia cells with differential effects. Importantly, the differential sensitivity of emodin, quercetin, and cis-stilbene between leukemia and normal cells suggests that polyphenols are potential therapeutic agents for leukemia.
authors.forename: Amani A
authors.initials: AA
authors.lastname: Mahbub
authors.forename: Christine L
authors.initials: CL
authors.lastname: Le Maitre
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Haywood-Small
authors.forename: Gordon J
authors.initials: GJ
authors.lastname: McDougall
authors.forename: Neil A
authors.initials: NA
authors.lastname: Cross
authors.affiliation: Sheffield Hallam University, Faculty of Health and Wellbeing, Sheffield, UK. N.Jordan-Mahy@shu.ac.uk.
authors.forename: Nicola
authors.initials: N
authors.lastname: Jordan-Mahy
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004642:Emodin / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008214:Lymphocytes / Q000187:drug effects* / Q000473:pathology; D015394:Molecular Structure; D022423:Myeloid Cells / Q000187:drug effects* / Q000473:pathology; D009928:Organ Specificity; D011794:Quercetin / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D013267:Stilbenes; D011794:Quercetin; D004642:Emodin